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Transcriptional regulation of A33 antigen expression by gut-enriched Krüppel-like factor

Oncogene volume 22, pages 4434–4443 (2003)Cite this article

Abstract

A33 antigen is a membrane-bound protein that is expressed only in intestinal epithelium and in most human colon cancers. Thus, A33 antigen has been explored as a potential therapeutic target for the treatment of colon cancers. However, little is known about the mechanism responsible for the tissue-specific pattern of its expression. In this report, we demonstrate that gut-enriched Krüppel-like factor (GKLF) binds to the promoter region of A33 antigen gene in colonic carcinoma cells and that mutations in the GKLF binding sequence in this region lead to diminished expression of A33 antigen. In addition, the expression of GKLF is linked to the expression of A33 antigen and blocking the expression of GKLF leads to the abolishment of A33 antigen expression. These results suggest that GKLF is a critical regulator in inducing the expression of A33 antigen in intestinal epithelium. While it has been suggested that GKLF is a regulator in inducing cell growth arrest and differentiation of the intestine, our observation that A33 antigen gene is a downstream target for GKLF suggests a more complex and diverse role for GKLF in the gut.

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Abbreviations

GKLF:

gut-enriched Krüppel-like factor

EGFP:

enhanced green fluorescent protein

EMSA:

electrophoretic mobility shift assays

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Acknowledgements

This work was supported by grants (30000199 to ZM and 30225043 to YS) from National Natural Science Foundation of China.

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  1. Zebin Mao and Song Shan: These authors contributed equally to the manuscript

Authors and Affiliations

  1. Depatrtment of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, 100083, China

    Zebin Mao, Song Shan, Yunyan Zhu, Xia Yi, Hua Zhang, Yongfeng Shang & Tanjun Tong

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  1. Zebin Mao
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Correspondence to Yongfeng Shang or Tanjun Tong.

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Mao, Z., Shan, S., Zhu, Y. et al. Transcriptional regulation of A33 antigen expression by gut-enriched Krüppel-like factor. Oncogene 22, 4434–4443 (2003). https://doi.org/10.1038/sj.onc.1206508

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